New combination therapy could deliver powerful punch to breast cancer

Nov 16, 2009
These are Drs. Kapil Bhalla (right) and Rekha Rao, assistant research scientist and first-author on the autophagy study presented this week. Credit: Medical College of Georgia

A powerful new breast cancer treatment could result from packaging one of the newer drugs that inhibits cancer's hallmark wild growth with another that blocks a primordial survival technique in which the cancer cell eats part of itself, researchers say.

While they are powerful killers of some breast , new drugs called histone deacetylase inhibitors, or HDAC inhibitors, also increase self-digestion, or autophagy, in surviving, mega-stressed cells, Medical College of Georgia Cancer Center researchers reported during the Molecular Targets and Cancer Therapeutics International Conference this week in Boston. The conference is sponsored by the American Association for Cancer Research, the National Cancer Institute and the European Organisation for Research and Treatment of Cancer.

"To meet the energy demands of growth and survival, cancer cells start eating up their own organelles, so that surviving cells become dependent on this autophagy," says Dr. Kapil Bhalla, director of the MCG Cancer Center.

"By also using autophagy inhibitors, we pull the rug out from under them. The only way out is death," he says.

Researchers showed the potent HDAC inhibitor panobinostat's impact on autophagy in human cells in culture as well as those growing in the mammary fat pads of mice. When they added the anti-malaria drug , which inhibits autophagy, breast cancer kill rates increased dramatically.

"As breast cancer is growing, it's developing these mechanisms of resistance to death," says Dr. Bhalla, Cecil F. Whitaker, Jr., M.D./Georgia Research Alliance Eminent Scholar in Cancer and Georgia Cancer Coalition Distinguished Cancer Scholar. "What we are saying is there is a new way to affect a resistant population."

Fundamentals of survival and growth put a lot of stress on cancer cells. Their drive for both comes from the activation of oncogenes and loss of that leaves cells looking desperately for ways to support their marching orders. Much like the extreme measures plane crash victims may take while stranded on a frozen mountaintop, autophagy becomes a survival strategy for the most stressed out cancer cells.

Stress kicks in as cancer cells quickly outgrow available blood supplies and nutrients, which stimulates new blood vessel formation and consumption of unprecedented amounts of fuel. Alterations in gene copy numbers create an imbalance in gene products or proteins adding to the stress of cancer cells, which are starting to make improperly folded - and functioning - proteins.

Protein degradation gets revved up and cells also start making more heat shock proteins which are supposed to help properly fold proteins and protect against cell death, a stress cause and effect Dr. Bhalla showed nearly a decade ago. He suspected then the connection he just found: promoting autophagy is one way heat shock proteins carry out their protective mission.

This is where HDAC inhibitors come into play: they promote acetylation or a modification in the key heat shock protein, hsp70, which further promotes autophagy. "Basically HDAC inhibitors promote acetylated hsp70 which promotes autophagy on which a stressed-out cancer cell depends," Dr. Bhalla says.

He notes that chloroquine, a known anti-malarial and inhibitor of autophagy, already is being paired with chemotherapy and radiation is some cancer clinical trials. But because of its significant side effects, new, more tolerable autophagy inhibitors need to be developed which can be combined with currently available anticancer agents, such as panobinostat, to attain superior therapeutic effect against breast , Dr. Bhalla says.

Source: Medical College of Georgia

Explore further: Chronic inflammation linked to 'high-grade' prostate cancer

add to favorites email to friend print save as pdf

Related Stories

Cell recycling protects tumor cells from anti-cancer therapy

Mar 06, 2008

Cells have their own recycling system: Discarded cellular components, from individual proteins through to whole cellular organs, are degraded and the building blocks re-used in a different place. The scientific term for this ...

Recommended for you

Unraveling the 'black ribbon' around lung cancer

Apr 17, 2014

It's not uncommon these days to find a colored ribbon representing a disease. A pink ribbon is well known to signify breast cancer. But what color ribbon does one think of with lung cancer?

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.